| Structural highlights
Function
MTX4_GRARO This cationic hydrophobic peptide inhibits a lot of different channels and has an antimicrobial activity. It blocks mechanosensitive ion channels (also named stretch-activated channels or SACs), without having effect on whole-cell voltage-sensitive currents. Acts by partitioning into the membrane and perturbing the interface between the channel and the lipid bilayer without necessarily being in physical contact with the channel. Inhibits atrial fibrillation as well as the membrane motor of outer hair cells at low doses. It also binds to the voltage sensor of voltage-gated potassium channels from the archaebacterium Aeropyrum pernix (KvAP) without affecting channel gating. It has also a medium toxicity on a large spectra of sodium channels (Nav1.1/SCN1A, Nav1.2/SCN2A, Nav1.3/SCN3A, Nav1.4/SCN4A, Nav1.5/SCN5A, Nav1.6/SCN8A, Nav1.7/SCN9A), and also inhibits potassium channels Kv11.1/KCNH2 and Kv11.2/KCNH6. It also exhibits antimicrobial activities against the Gram-positive bacteria B.subtilis (MIC=0.5 uM), S.aureus (MIC=2-4 uM), and S.epidermidis (MIC=4-8 uM), and Gram-negative bacteria S.typhimurium (MIC=32.64 uM), P.aeruginosa (MIC=8-16 uM), and E.coli (MIC=8-16 uM).[1] [2] [3] [4] [5] [6] [7] [8] [9]
References
- ↑ Suchyna TM, Johnson JH, Hamer K, Leykam JF, Gage DA, Clemo HF, Baumgarten CM, Sachs F. Identification of a peptide toxin from Grammostola spatulata spider venom that blocks cation-selective stretch-activated channels. J Gen Physiol. 2000 May;115(5):583-98. PMID:10779316
- ↑ Bode F, Sachs F, Franz MR. Tarantula peptide inhibits atrial fibrillation. Nature. 2001 Jan 4;409(6816):35-6. PMID:11343101 doi:http://dx.doi.org/10.1038/35051165
- ↑ Suchyna TM, Tape SE, Koeppe RE 2nd, Andersen OS, Sachs F, Gottlieb PA. Bilayer-dependent inhibition of mechanosensitive channels by neuroactive peptide enantiomers. Nature. 2004 Jul 8;430(6996):235-40. PMID:15241420 doi:http://dx.doi.org/10.1038/nature02743
- ↑ Ruta V, MacKinnon R. Localization of the voltage-sensor toxin receptor on KvAP. Biochemistry. 2004 Aug 10;43(31):10071-9. PMID:15287735 doi:http://dx.doi.org/10.1021/bi049463y
- ↑ Jung HJ, Kim PI, Lee SK, Lee CW, Eu YJ, Lee DG, Earm YE, Kim JI. Lipid membrane interaction and antimicrobial activity of GsMTx-4, an inhibitor of mechanosensitive channel. Biochem Biophys Res Commun. 2006 Feb 10;340(2):633-8. Epub 2005 Dec 19. PMID:16376854 doi:http://dx.doi.org/10.1016/j.bbrc.2005.12.046
- ↑ Fang J, Iwasa KH. Effects of tarantula toxin GsMTx4 on the membrane motor of outer hair cells. Neurosci Lett. 2006 Aug 14;404(1-2):213-6. Epub 2006 Jun 22. PMID:16797839 doi:http://dx.doi.org/S0304-3940(06)00548-9
- ↑ Nishizawa M, Nishizawa K. Molecular dynamics simulations of a stretch-activated channel inhibitor GsMTx4 with lipid membranes: two binding modes and effects of lipid structure. Biophys J. 2007 Jun 15;92(12):4233-43. Epub 2007 Mar 23. PMID:17384064 doi:http://dx.doi.org/10.1529/biophysj.106.101071
- ↑ Posokhov YO, Gottlieb PA, Morales MJ, Sachs F, Ladokhin AS. Is lipid bilayer binding a common property of inhibitor cysteine knot ion-channel blockers? Biophys J. 2007 Aug 15;93(4):L20-2. Epub 2007 Jun 15. PMID:17573432 doi:http://dx.doi.org/10.1529/biophysj.107.112375
- ↑ Redaelli E, Cassulini RR, Silva DF, Clement H, Schiavon E, Zamudio FZ, Odell G, Arcangeli A, Clare JJ, Alagon A, de la Vega RC, Possani LD, Wanke E. Target promiscuity and heterogeneous effects of tarantula venom peptides affecting Na+ and K+ ion channels. J Biol Chem. 2010 Feb 5;285(6):4130-42. doi: 10.1074/jbc.M109.054718. Epub 2009, Dec 2. PMID:19955179 doi:http://dx.doi.org/10.1074/jbc.M109.054718
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